Bench to Bedside: Drug-Coated Balloons, New Imaging Modalities for Atherosclerosis, and Other Advances
The session opened up with a discussion of the emerging field of renal denervation therapies as presented by Juan F. Granada, MD, a cardiologist at the Skirball Center for Cardiovascular Research in New York. This is a catheter-based method used to treat resistant hypertension patients. The renal denervation method involves application of radio waves to renal arteries, which then causes a reduction in afferent and efferent renal sympathetic nerve activities. While this technology effectively reduces hypertension, there have been major problems up until recently with unwanted side effects in past research. Currently the field has advanced rapidly, but large gaps still remain in the basic understanding of this technology and clinical trials are expected to be initiated soon.
One of the underappreciated aspects of drug eluting stents (DESs) is the fact that no matter which drug is used, there appears to be an atherogenic quality with DESs that is not seen with bare metal stents. Dr Granada concurred. In a talk entitled, “Pathology and Mechanisms of Late Thrombotic Events Due to Neoatherosclerosis in Drug Eluting Stents,” Aloke V. Finn, MD, a cardiologist with Emory University, Georgia, elaborated on newly elucidated details for the pathway connecting DES with neoatherosclerotic events. Basically first generation mTor inhibitors cause increases in intracellular calcium through binding to the FK506-binding protein, FKBP12, leading to impaired endothelial membrane function, which results in neointimal lipid deposits. Second generation mTor inhibitors do not work via binding to FKBP12 and do not increase intracellular calcium. So these newer mTor inhibitors are under investigation as potentially superior components of DESs.
The next 2 talks focused on intravascular imaging. Jarouc Jaffer, MD, of Harvard Medical School discussed “Intravascular Molecular Imaging of Inflamed Plaques and Stents.” The general goal has been to apply intravascular imaging to predict high-risk plaques in advance of any disease events. Initial studies from the PROSPECT clinical trials provided positive hazard ratio (HR) statistics for using VH intravascular ultrasound imaging (IVUS), however, the per plaque HR was not so great. New technologies were developed to enable molecule-specific visualization within the vessels. The technology uses near infrared fluorescence imaging simultaneously with optical frequency domain imaging (NIRF-OFDI). Injection of tracers enabled the specific molecular detection of cathepsin B or fibrin intravascular in the presented examples. With these advances in technology they were able to identify individual high-risk plaques in a quantitative fashion and Dr Jaffer anticipates this technology may be a useful tool for increasing our understanding of the mechanism by which DESs are atherogenic as described above.
A similar technology involving near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) was rigorously examined for potential high-risk predictive value with histological assessments in a presentation offered by Robert L. Wilensky, MD, a cardiologist at the Pennsylvania School of Medicine. Dr Wilensky showed that they were able to obtain in vivo anatomic and biochemical prediction for specific atherosclerotic lesions using this technology. NIRS positive fibroatheromas had thinned fibrous caps with increased plaques. Persistent lipid core plaques predicted progressive plaque development with larger necrotic core size.
In summary, renal denervation for the relief of resistant hypertension continues to be a developing area of active research. Huge strides have been made in increasing our ability to visualize individual plaques with predictive value for determining which ones are high risk. New mTor inhibitors may improve the healing effectiveness of DESs. The presentations were optimistic, thorough in analysis, and indicate that all of these fields are moving in positive and significant direction towards improving interventional medicine.